Every patient in a small clinical trial at Memorial Sloan Kettering Cancer Center saw their rectal cancer vanish after receiving a single immunotherapy drug, with no surgery, no radiation, and no chemotherapy. The drug, dostarlimab, produced a 100% clinical complete response rate in patients with locally advanced rectal cancer whose tumors carried a genetic trait called mismatch repair deficiency, or dMMR. First reported in 2022 and reinforced by longer follow-up data published since, the results remain one of the most striking outcomes in modern oncology. But the trial’s small size and narrow patient selection mean the findings are a starting point, not a finish line.
What the trial showed
The phase 2 study, registered as NCT04165772, tested a strategy called neoadjuvant PD-1 blockade. Patients with stage II or III dMMR rectal cancer received dostarlimab (brand name Jemperli, manufactured by GSK) before any conventional treatment. The drug blocks PD-1, a protein that cancer cells exploit to evade the immune system. In dMMR tumors, which accumulate unusually high numbers of DNA mutations because their internal error-correction machinery is broken, removing that shield can unleash a powerful immune attack.
Initial results, published in the New England Journal of Medicine in June 2022, reported that all 14 patients treated at that point achieved complete clinical responses. None went on to receive chemoradiation or surgery. A subsequent peer-reviewed update in the same journal extended the analysis with longer follow-up and additional patients, including data on other resectable dMMR solid tumors. For the rectal cancer group specifically, no recurrences had been detected at the time of that report, reinforcing the durability of the responses over the available observation period.
The trial was single-arm, meaning there was no comparison group receiving standard therapy. Endpoints included clinical and pathological complete response, assessed through endoscopy, MRI, and digital rectal examination on a defined schedule outlined in the trial protocol.
Why organ preservation matters
Standard treatment for locally advanced rectal cancer typically involves weeks of radiation, concurrent chemotherapy, and major surgery that can permanently alter bowel, bladder, and sexual function. Many patients face the possibility of a permanent colostomy bag. Recovery is long, and the psychological toll extends well beyond the operating room.
For the roughly 5% to 10% of rectal cancer patients whose tumors are dMMR, according to estimates in published oncology literature, dostarlimab offered a different path in this trial. Participants avoided every component of standard treatment and instead entered close surveillance to watch for any sign of regrowth. Within the constraints of this small, carefully selected group, the data suggest that immunotherapy alone can produce deep remissions while sparing patients from life-altering side effects.
Regulatory scrutiny and open questions
The U.S. Food and Drug Administration took a close look at the evidence in February 2023, when its Oncologic Drugs Advisory Committee reviewed dostarlimab’s potential use in treatment-naive dMMR locally advanced rectal cancer. Briefing documents from that meeting laid out the agency’s concerns: the absence of a randomized control arm, limited long-term follow-up, and the need for data from a broader, more diverse patient population that better reflects differences in age, ethnicity, comorbidities, and access to specialized cancer centers.
As of April 2026, dostarlimab holds FDA approval under the Jemperli brand for certain dMMR solid tumor indications, but a specific approval for frontline use in locally advanced rectal cancer as a surgery-replacing strategy has not been granted. Confirmatory trials with larger enrollment and longer observation periods are expected to inform future regulatory decisions.
Several scientific questions also remain unresolved. The most pressing is durability: whether these remissions will hold at five, ten, or twenty years is unknown. Late relapses occur in some cancers, and only extended follow-up can determine whether immunotherapy alone matches the long-term cure rates achieved by surgery-based approaches. Clinicians must weigh the appeal of avoiding surgery against the risk, however small it currently appears, of undertreating a curable disease.
Quality-of-life data, detailed side-effect profiles, and demographic breakdowns of trial participants have not been fully reported in the primary publications. That gap matters because immune-related adverse events, including colitis, thyroid dysfunction, and skin reactions, can be serious and sometimes permanent. Their incidence in this specific setting has not been described with the same depth seen in larger metastatic cancer trials.
The single-arm design also makes it impossible to know how much of the outcome is attributable to dostarlimab versus the natural biology of dMMR tumors, which are inherently more visible to the immune system. Some dMMR rectal cancers respond well even to standard chemoradiation, raising the question of whether a subset of these patients might have achieved similar results without immunotherapy. Only randomized or carefully matched comparative studies can answer that.
Where the science stands now
The strongest evidence supporting this story comes from two peer-reviewed reports in the New England Journal of Medicine and the official trial registration on ClinicalTrials.gov. Together, they confirm the core finding: in a small, biomarker-selected dMMR rectal cancer population treated at an expert center, dostarlimab monotherapy produced complete clinical responses in every reported case over the initial follow-up window. FDA briefing documents add regulatory context, highlighting what additional proof is needed before this approach could reshape standard care.
What the evidence does not yet support is a broad claim that immunotherapy can replace surgery for all rectal cancer patients. The findings apply only to tumors with mismatch repair deficiency, a minority of cases, and even within that group the data come from a modest number of patients treated under highly controlled conditions.
For patients with dMMR rectal cancer, participation in clinical trials exploring immunotherapy-based organ preservation may be a compelling option, particularly at centers experienced in nonoperative management. For the broader rectal cancer population, established multimodality therapy remains the proven standard. The dostarlimab trial is best understood as a powerful signal of what targeted immunotherapy might achieve in the right patients, and a catalyst for the larger studies that will determine whether that signal holds.
More from Morning Overview
*This article was researched with the help of AI, with human editors creating the final content.
